Indications

Methamphetamine is one of the powerful stimulants of the central nervous system (CNS). It is sometimes used as a second-line treatment for attention deficit hyperactivity disorder and obesity; however, methamphetamine is better known as a recreational drug.

Methamphetamine was first discovered in 1893 from two chemical subgroups: dextromethamphetamine and levomethamphetamine. After 2 decades, in 1919 methamphetamine originated from amphetamine in Japan. Later in the 1930s, the drug was introduced to the United States as a bronchial inhaler and a nasal decongestant. Later, it was used to treat obesity. Overall, the use of the term methamphetamine refers to an equal mixture of dextromethamphetamine and levomethamphetamine in their pure amine forms. Prescribing this medication is limited due to its neurotoxic potential and risk of recreational use as a euphoriant. Today, there are safer medications of choice with the same treatment efficacy, and hence, the use of methamphetamines in the United States is very limited.[1]

Due to illicit trafficking and recreational use of racemic methamphetamine, levomethamphetamine, and dextromethamphetamine, the agent is classified as a schedule II, controlled substance in the United States and the United Nations Convention on Psychotropic Substances.[2]

Because of the easy chemical process of synthesis of methamphetamine, it can be easily produced illicitly in meth-labs nationwide.[3] Illegal laboratories and larger super-labs across the United States, particularly in California (Central Valley), Arizona, Utah, and Texas have been discovered over the past 3 decades. The growth of Mexico-based traffickers and the expansion of independent illegal labs, methamphetamine is mass manufactured in many places today in the Pacific Northwest, Midwest, and some parts of the southeast and the northeast United States.[4]

The use of methamphetamine in higher doses can induce psychosis, bleeding in the brain, skeletal muscle breakdown, and seizures. Moreover, when it is used chronically, it can cause violent behavior, mood swings, and psychosis such as paranoia, delirium, auditory and visual hallucination, and delusions.

Chronic long-term methamphetamine use can be highly addictive, and if it discontinued abruptly, may lead to withdrawal symptoms that can be persistent for months after use.

Mechanism of Action

Methamphetamine affects the central nervous system (CNS) by enhancing the release of monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine. [7] Use of methamphetamine can lead to many pharmacological effects because of its ability to use various molecular processes. Methamphetamine causes the levels of monoamines to be increased by:

Discharging the monoamines out of their storage and freeing them into the synaptic space by making reversal action of the dopamine transporters

Obstructing the reuptake of monoamines by preventing the activity of transporters of monoamine[6]

Methamphetamine can increase expression of CRE-Luc by TAAR1 in transfected cells. Methamphetamine interacts with TAAR1 which triggers a definite inhibition in dopamine uptake dependent to TAAR1 in transfected cells. Methamphetamine has a similar effect in brain striatal synaptosomes.[8][9]

Reducing the dopamine transporters expressions at the cell surface

The proliferation of the cytosolic levels of monoamines by inhibiting the monoamine oxidase activity

Enhancing the expression and activity of the dopamine-synthesizing enzyme tyrosine hydroxylase[10]

Methamphetamine is highly lipid soluble that helps to be transferred relatively fast across the blood-brain barrier and has an immediate effect on CNS.[2]

Administration

Methamphetamine can be ingested orally, through intravenous injection, smoked, and snorted.

Adverse Effects

People who use methamphetamine feel an acute, powerful short rush for about 5 to 30 minutes which varies based on different routes of use. The drug also causes the enhance energy level, decreases appetite, and creates euphoria for a range of 6 to 12 hours.

Short-Term Effects

Decreased appetite

Nausea

Psychosis

Tachycardia

Hypertension

Increased body temperature

Panic attack

Mydriasis (Dilation of pupils)

Disturbed sleep patterns

Violent, bizarre, and erratic behavior

Hallucinations and irritability

Seizures, convulsions, and death from high doses

Long-Term Effects

Long-lasting damage to blood vessel of heart and brain

Lung, liver, and kidney damage

Hypertension that can lead to heart attacks, strokes and death

Severe tooth degeneration

In case of sniffed, destruction of soft-tissues in nose

In case of smoking, respiratory problems

In case of injections, infectious diseases, cellulitis, and abscesses

Weight loss and malnutrition

Disorientation, apathy, confusion and exhaustion

Severe psychological dependence

Psychosis

Depression

Damage to the brain structure similar to Alzheimer’s disease, epilepsy, and stroke

Tweaking:

The last stage of methamphetamine abuse happens when the person who abuse methamphetamine become paranoid and irritable because of lack of sleep for about 3 to 15 days. This behavior is called "tweaking," and the person with this behavior is known as the "tweaker." Usually, tweakers continue to require more methamphetamine to get to the original high.[12] This is difficult to achieve, which causes frustration and irritability and unsteady behavior in the tweaker. Because tweakers are unpredictable, they can behave violently, can get involved in domestic arguments, spur-of-the-moment offenses, and become a danger to others or themselves.[13]

A tweaker can behave normally and have clear eyes, concise speech, and brisk movements; however, careful observation will indicate that the person's eye movement is much faster than normal (up to 10 times), and they have a minor quiver voice and jerky movements. Some tweakers minimize or cover these physical symptoms by using a depressant like alcohol or opioids; however, use of a depressant by the tweaker increases his or her negative feelings of paranoia, irritability, and frustration significantly. Other people around these users should use extreme caution because of their unpredictable behaviors.[3]

Contraindications

Having thoughts of suicide

Tourette syndrome

Hyperthyroidism

Bipolar disorder

Psychotic disorder

Drug abuse

Behaving with excessive cheerfulness or activity

Chronic muscle twitches or movements

Aggressive behavior

Increased ophthalmic pressure

Hypertension

History of a heart attack

Coronary artery disease

Cardiomyopathy

Arrhythmia

Chronic heart failure

Stroke

Atherosclerosis

Numbness

Prickling

Tingling of fingers and toes

Seizures

Loss of appetite

Weight loss

Breastfeeding mothers

Increased cardiovascular event risk

Structural disorder of the heart

Chronic kidney disease stage 4 (severe) or 5 (failure)

Kidney disease with a likely reduction in kidney function

Allergic reaction to sympathomimetic agents or amphetamine analogues

Monitoring

Methamphetamine users have different symptoms that can be recognized, for example, lack of sleep (insomnia), acute anxiety, agitation, and psychotic or violent behavior. If these types of behavior develop after using the methamphetamine, the meth use may have developed dependency. Chronic meth users also usually show poor personal hygiene, and sores on their bodies from picking at "crank bugs," unhealthy complexion, a pale, and tactile hallucination that often seen in tweakers. Methamphetamine users may develop cracked teeth because of extreme clenching of their jaw during the time being high on methamphetamine.

Toxicity

Use of methamphetamine can cause physical and psychological dependence and increased tolerance. Because of the rapid development of tolerance, methamphetamine users frequently need to increase the dose to get to the satisfying "high" which can be very dangerous because administration of too much methamphetamine also increases the risk of an overdose.[15] Based on the reports from 2011, more than 102,000 emergency department visits in the United States were related to methamphetamine use, with over 50% of users also using a combination of other drugs such as alcohol and marijuana, thus producing a synergistic effect. Knowing the physical and behavioral symptoms of the methamphetamine overdose, and diagnosis of the toxicity is important for saving the patient’s life.[16]

Acute: When methamphetamine users experience an adverse reaction due to use a large amount of methamphetamine one time; can be fatal sometimes.

Chronic: Result of many negative health effects of chronic methamphetamine abuse[17]

Signs and symptoms of methamphetamine toxicity:

Mydriasis (dilated pupils)

Bradycardia or tachycardia

Irregular heart rhythm (arrhythmia)

Chest pains

Shortness of breath

Increased body temperature

Heart attack

Hypertension

Kidney damage

Altered mental status.

Gastrointestinal distress

Agitation, violent, psychotic behaviors

Patients who experience methamphetamine toxicity usually presenting with an altered mental status that can show as psychotic episodes, irritability, suicidal ideation, and rarely coma or seizures.

Some patients present with psychotic symptoms, including tactile hallucinations and severe paranoia.

Chronic long-term methamphetamine use can also cause dental complications, significant weight loss, and skin problems such as sores and abscesses.[4]

Enhancing Healthcare Team Outcomes

Due to the unpredictable behaviors, irritability, and the possibility of psychotic behavior of methamphetamine users especially during the hospital visit due to the overdose, or complication, the safety of medical and security staff are important. Hence, it is always advised to use precautions when dealing with these patients. Another healthcare worker or security personnel should always accompany these patients. The triage nurse should be fully aware of the adverse effects of amphetamine and ensure that the emergency department is fully aware of the individual admitted.

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Methamphetamine - Questions

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A patient presents to the emergency department with agitation, mydriasis, hypertension, and tachycardia. He states that he snorted "some crystals" with friends and that he feels energetic and anxious. He reports that his friends told him this is a treatment for weight loss and this is the reason why he tried it. Which is true of the drug most likely used by this patient?

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A 30-year-old female with no past medical history came to the emergency department with agitation, and chest pain. During the interview, she is irritable, and her speech is fast with labile tone. there is psychomotor agitation. Her blood pressure is 160/90 mmHg, and heart rate 130 bpm. On physical examination, her pupils are 5 mm. There is poor oral hygiene including gum atrophy and cracked on her teeth. There are multiple reddish skin marks all over the body. The patient is paranoid about every recommendation that medical staff offers and became argumentative with staff. If substance use is the reason for her presentation, what is the most important question to ask from the patient to rule out the tweaking stage?

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